crossing96/oncoscreening huggingface dataset:
Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis.	Cancer stem cells (CSCs) are a sub-population of tumor cells playing essential roles in initiation, differentiation, recurrence, metastasis and development of drug resistance of various cancers, including bladder cancer. Although multiple lines of evidence suggest that metformin is capable of repressing CSC repopulation in different cancers, the effect of metformin on bladder cancer CSCs remains largely unknown. Using the N-methyl-N-nitrosourea (MNU)-induced rat orthotropic bladder cancer model, we demonstrated that metformin is capable of repressing bladder cancer progression from both mild to moderate/severe dysplasia lesions and from carcinoma in situ (CIS) to invasive lesions. Metformin also can arrest bladder cancer cells in G1/S phases, which subsequently leads to apoptosis. And also metformin represses bladder cancer CSC repopulation evidenced by reducing cytokeratin 14 (CK14+) and octamer-binding transcription factor 3/4 (OCT3/4+) cells in both animal and cellular models. More importantly, we found that metformin exerts these anticancer effects by inhibiting COX2, subsequently PGE2 as well as the activation of STAT3. In conclusion, we are the first to systemically demonstrate in both animal and cell models that metformin inhibits bladder cancer progression by inhibiting stem cell repopulation through the COX2/PGE2/STAT3 axis.	bladder
[Effect of synthetic small double-stranded RNA on the development of bladder cancer by activating P21 expression].	OBJECTIVE: To investigate the effects of a synthetic small double-stranded RNA (dsRNA) dsP21-555 on the development of bladder cancer cell lines T24 and EJ. METHODS: According to the different treatments, bladder cancer cells were divided into three groups: negative control group (transfected with dsControl), positive control group (transfected with candidate microRNA, i.e. miR-370) and experimental group (transfected with dsP21-555). Real-time fluorescent quantitative polymerase chain reaction (qPCR) was conducted to detect the expressions of p21 mRNA and cyclin-dependent kinases 4/6 (CDK4/6) mRNA; Western blot was operated to verify the expression of P21 and CDK4/6 proteins. Cell cycle distribution was measured by flow cytometry after transfection. Cell proliferation assay was performed to evaluate the proliferative capacity of transfected cells. Colony formation assay was carried out to analyze the proliferative ability of single cancer cells. RESULTS: qPCR showed that, compared with the negative control group, dsP21-555 up-regulated the expressions of p21 mRNA by 2.46 times (P<0.01) in T24 cells and 2.60 times (P<0.01) in EJ cells; compared with the positive control group, the expression of p21 mRNA was no significantly different in the experimental group (P>0.05). Compared with the dsControl group, dsP21-555 suppressed the expressions of CDK4 mRNA by 43% (P<0.01) in T24 and 54% (P<0.01) in EJ cells, the expression of CDK6 mRNA by 39% (P<0.01) in T24 and 36% (P<0.01) in EJ cells; the differences in the expression of CDK4 and CDK6 mRNAs between the miR-370 and dsP21-555 groups were not statistically significant (P> 0.05). Western blot verified the differences of p21 and CDK4/6 genes expression among groups. Flow cytometry revealed that the G0/G1 phase cells significantly increased while S and G2/M phase cells decreased in the miR-370 and the dsP21-555 groups, compared with the dsControl group. Cell proliferation assay showed that, compared with the dsControl group, the proliferative capacities of cells transfected with miR-370 or dsP21-555 decreased significantly (both P<0.05), but the difference in proliferative capacities between the miR-370 and the dsP21-555 groups was no statistically significant (P>0.05). Colony formation assay showed that the numbers of colonies formed in the miR-370 and the dsP21-555 groups were both smaller than that in the dsControl group. CONCLUSION: dsP21-555 may activate the expression of P21 protein by RNA activation, thereby significantly inhibit the growth of bladder cancer cells.	bladder
Extended versus superextended lymph-node dissection in radical cystectomy: subgroup analysis of possible recurrence-free survival benefit.	Objective The aim of this study was to assess potential benefits of different extended lymph-node dissection templates at the time of radical cystectomy as treatment for invasive bladder cancer. Materials and methods Between 2004 and 2012, 578 patients underwent radical cystectomy with lymph-node dissection without prior radiotherapy or chemotherapy. Two different historical cohorts were constructed: 262 patients underwent intended superextended lymph-node dissection (seLND) from January 2004 to January 2009 and 316 patients underwent intended extended lymph-node dissection (eLND) from February 2009 to December 2012. Recurrence-free survival (RFS) was analysed as the primary outcome. Median follow-up was 93 (63-123) months and 38 (16-63) months in the two groups, respectively. Results There was no significant difference in RFS in the two cohorts (p = 0.87). When analysed according to lymph-node status (N0 or N+), there was no significant difference in RFS between the two cohorts in the two subgroups (p = 0.41 and p = 0.48, respectively). When analysed according to tumour stage, patients with non-organ-confined disease revealed a tendency towards better RFS in the seLND cohort (p = 0.14). This tendency was most clearly seen in the subgroup of T3-4 patients without lymph-node metastases (N0) (p = 0.14). Conclusions Extending LND up to the inferior mesenteric artery (seLND) does not seem to be beneficial to the overall population of patients with invasive bladder cancer compared to performing an eLND to the aortic bifurcation only. However, a subgroup of patients with non-organ-confined disease without macrometastases may benefit from seLND.	bladder
Retrospective analysis of palliative chemotherapy for the patients with bladder adenocarcinoma: Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee.	BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.	bladder
Potential of sulfasalazine as a therapeutic sensitizer for CD44 splice variant 9-positive urogenital cancer.	Cancer stem-like cells (CSCs) with high expression of CD44 splice variant (CD44v) have an enhanced capacity for intracellular reduced glutathione synthesis and defense against reactive oxygen species, resulting in resistance to various therapeutic stresses. Sulfasalazine (SSZ), a drug used in the treatment of rheumatoid arthritis (RA), inhibits glutamate-cystine transport, and suppressed CD44v-dependent tumor growth and increased sensitivity to cytotoxic drugs in an in vivo study. Here, we present two cases of CD44v9-positive urogenital cancer with concomitant treatment with SSZ for RA. Patient 1 was a 62-year-old man who had received SSZ for RA beginning 2 months before the diagnosis of urinary bladder cancer. Although he had multiple metastases to the bladder, abdominal, left cervical and left axillary lymph nodes, and brain, complete response with multidisciplinary therapy was maintained for more than 2 years. Patient 2 was a 74-year-old man with castration-resistant prostate cancer who was diagnosed with RA during chemotherapy and a gradual increase in prostate-specific antigen (PSA) level. When SSZ was added, his PSA value (ng/mL) decreased from 12.93 to 5.58 in only 2 weeks and then quickly rebounded, whereas levels of neuron-specific enolase, a neuroendocrine differentiator and CSC marker, remained almost unchanged. We therefore speculate that SSZ treatment may represent a new adjuvant treatment option for patients with CD44v9-positive urogenital cancer.	bladder
Change in Management Based on Pathologic Second Opinion Among Bladder Cancer Patients Presenting to a Comprehensive Cancer Center: Implications for Clinical Practice.	OBJECTIVE: To evaluate the incidence and degree of change from a pathologic second opinion of bladder biopsies at a Comprehensive Cancer Center that were initially performed at referring community hospitals. The secondary objective was to determine the impact the potential changes would have on a patient's treatment. MATERIALS AND METHODS: Dedicated genitourinary pathologists reviewed 1191 transurethral biopsies of the bladder and/or prostatic urethra from 2008 to 2013. Major and minor treatment changes were defined as altering recommendations for cystectomy, systemic chemotherapy, or primary cancer diagnosis, and alterations in intravesical regimens, respectively. RESULTS: There were 326/1191 patients (27.4%) with a pathologic change on second opinion: grade (62/1191, 5.2%), stage (115/1191, 9.7%), muscle in the specimen (29/1191, 2.4%), presence or absence of carcinoma in situ (34/1191, 2.9%). Outside pathology did not address the presence or absence of lymphovascular invasion in 620/759 (81.7%) of invasive cases (≥cT1), of which 35/620 (5.6%) had lymphovascular invasion. There were 212 mixed, variant, or nonurothelial histologies detected in 199/1191 (16.7%) patients, with 114/212 (53.7%) resulting in reclassification by our pathologists. Potential treatment alterations accounted for 182/1191 (15.3%) of cases, with 141/1191 (11.8%) imparting major changes. There were 82/1191 (6.8%) changes in recommendation for a radical cystectomy, 38/1191 (3.2%) had a complete change in primary tumor type, and 21/1191 (1.8%) for change in chemotherapy regimen. CONCLUSION: The amount and degree of pathologic changes and its potential impact on treatment emphasize the importance of bladder cancer patients having their histology reviewed by genitourinary-dedicated pathologists. In our cohort, 15.3% of patients could see a treatment alteration, with 11.8% being a major change.	bladder
Bladder cancer diagnosis from bladder wash by Fourier transform infrared spectroscopy as a novel test for tumor recurrence.	This study proposes Fourier Transform Infrared (FTIR) spectroscopy as a more sensitive, rapid, non-destructive and operator-independent analytical diagnostic method for bladder cancer recurrence from bladder wash than other routinely used urine cytology and cystoscopy methods. A total of 136 patients were recruited. FTIR spectroscopic experiments were carried out as a blind study, the classification results of which were then compared with those of cytology and cystoscopy. Firstly, 71 samples (n = 37; bladder cancer and n = 34; control) were studied with transmittance FTIR spectroscopy. After achieving successful differentiation of the groups, to develop a more rapid diagnostic tool and check the reproducibility of the results, the work was continued with different samples (n = 65 as n = 44; bladder cancer and n = 21; control), using the reflection mode (ATR) of FTIR spectroscopy by a different operator. The results revealed significant alterations in moleculer content in the cancer group. Based on the spectral differences, using transmittance FTIR spectroscopy coupled with chemometrics, the diseased group was successfully differentiated from the control. When only carcinoma group was taken into consideration a sensitivity value of 100% was achieved. Similar results were also obtained by ATR-FTIR spectroscopy. This study shows the power of infrared spectroscopy in the diagnosis of bladder cancer.	bladder
Neutrophil-to-lymphocyte ratio as a detection marker of tumor recurrence in patients with muscle-invasive bladder cancer after radical cystectomy.	PURPOSE: High-neutrophil to lymphocyte ratio (NLR) values have been shown to be associated with a poor prognosis in many human malignant tumors. We evaluated the correlation of the NLR with other variables in patients with muscle-invasive bladder cancer after radical cystectomy (RC); in particular, we evaluated chronological changes in the postoperative NLR. METHODS: We included the data from a total of 110 patients who underwent RC for muscle-invasive bladder cancer. The NLR was calculated using complete blood counts determined before RC. Kaplan-Meier and Cox proportional regression analyses of recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were performed to identify significant prognostic variables. RESULTS: The median patient age was 72 years (41-91 years). In univariate analysis, the pretreatment NLR (≥2.6 vs.<2.6) was associated with RFS (hazard ratio [HR] = 2.41, P = 0.008), CSS (HR = 2.89, P = 0.006), and OS (HR = 2.73, P = 0.002). In multivariate analysis, an NLR≥2.6 and an infiltrative growth pattern at the tumor invasion front were significantly associated with RFS (HR = 2.61, P = 0.023), CSS (HR = 2.58, P = 0.08), and OS (HR = 2.77, P = 0.004). Postoperative chronological analysis revealed that the NLR of 68 patients without recurrence remained low during follow-up, whereas the NLR of the remaining 42 patients with recurrence increased significantly in the last visit before recurrence was detected radiographically (P< 0.01). CONCLUSIONS: The NLR and tumor growth pattern were strong predictors of prognosis for patients undergoing RC. Our results suggest that an increase in the NLR during follow-up after RC is a potential marker for the early detection of recurrence.	bladder
HER2 Protein Overexpression and Gene Amplification in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder.	AIM: HER2 overexpression has been reported in a minority of urothelial carcinomas, but little is known about HER2 protein expression and gene alterations in plasmacytoid urothelial carcinoma, a rare and aggressive variant. The aim of this study was to clarify the HER2 status in plasmacytoid urothelial carcinomas. METHODS: Six cases of plasmacytoid urothelial carcinoma were included, in which we evaluated HER2 protein expression by immunohistochemistry (IHC) and HER2 gene amplification by fluorescence in situ hybridization (FISH). RESULTS: The patients' ages ranged from 57 to 83 years (mean age, 71 years). Five patients were male and one was female. The ratio of the plasmacytoid component ranged from 30% to 100% (mean, 77%). HER2 expression score was 3+ in 4 cases, 2+ in one case, and negative in one case. HER2 gene amplification was positive in 3 cases, of which 2 cases showed a 3+ HER2 IHC score but one case was negative for HER2 IHC. Another 2 cases showed equivocal HER2 FISH results, and one remaining case was negative for HER2 FISH. CONCLUSION: Our observation that plasmacytoid urothelial carcinomas frequently demonstrated HER2 protein overexpression provides supporting evidence that HER2 may be a potential therapeutic target for plasmacytoid urothelial carcinoma.	bladder
[Clinicopathologic features of solitary fibrous tumor in urogenital system].	OBJECTIVE: To study the clinicopathologic features and differential diagnosis of solitary fibrous tumor (SFT) in the urogenital system. METHODS: The clinical data and pathologic characteristics of eight cases of SFT in the urogenital system were analyzed, and the relevant literature was reviewed. RESULTS: The cohort included six male and two female patients, with age of onset ranging from 25 to 80 years. Five occurred in the kidney (three in the right kidney), one case each occurred in the bladder, the prostate and the spermatic cord. Most patients showed no obvious clinical symptoms or only had low back pain and swelling. The diameter of the tumor was ranged from 2.5 to 11.8 cm (median 5.2 cm). Microscopy showed at low magnification, the tumor cells were spindle-shaped and arranged in bundles or helicoid pattern. The regional mesenchymal fibroblasts showed hyperplasia, with obvious collagenization and formed hemangiopericytoma-like structure. One case showed increased mitotic figures (>5 cells/10 HPF) and focal necrosis. By immunohistochemistry, the tumor cells were positive for CD34 and STAT6 in all eight cases, CD99 and vimentin in six cases, bcl-2 in four cases and SMA in one case. All seven cases with follow-up did not show any tumor recurrence or metastasis. CONCLUSIONS: SFT is rare in the urogenital system and most patients show good prognosis. SFT expresses CD34 and STAT6 and needs to be distinguished from other spindle cell tumors.	bladder
Nonoccupational exposure to agricultural work and risk of urinary bladder cancer among Egyptian women.	This study examined the associations between nonoccupational exposure to agricultural work, through husband or head of household (H/HH) occupation, and urinary bladder cancer risk among Egyptian women. A total of 1,167 women (388 bladder cases and 779 age- and residence-matched, population-based controls) from a multicenter case-control study were included in the analysis. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic regression. Among married women, those who reported H/HH to be an agricultural worker were at increased risk for bladder cancer as compared to those with H/HH in other occupations, AOR = 1.54, 95% CI [1.09, 2.18]; among unmarried women the risk was not increased, AOR = 0.77, 95% CI [0.45, 1.32]. Nonoccupational exposure to agricultural work, defined as living with an agricultural worker, increased the risk for bladder cancer among married Egyptian women.	bladder
MiRImpact, a new bioinformatic method using complete microRNA expression profiles to assess their overall influence on the activity of intracellular molecular pathways.	MicroRNAs (miRs) are short noncoding RNA molecules that regulate expression of target mRNAs. Many published sources provide information about miRs and their targets. However, bioinformatic tools elucidating higher level impact of the established total miR profiles, are still largely missing. Recently, we developed a method termed OncoFinder enabling quantification of the activities of intracellular molecular pathways basing on gene expression data. Here we propose a new technique, MiRImpact, which enables to link miR expression data with its estimated outcome on the regulation of molecular pathways, like signaling, metabolic, cytoskeleton rearrangement, and DNA repair pathways. MiRImpact uses OncoFinder rationale for pathway activity calculations, with the major distinctions that (i) it deals with the concentrations of miRs--known regulators of gene products participating in molecular pathways, and (ii) miRs are considered as negative regulators of target molecules, if other is not specified. MiRImpact operates with 2 types of databases: for molecular targets of miRs and for gene products participating in molecular pathways. We applied MiRImpact to compare regulation of human bladder cancer-specific signaling pathways at the levels of mRNA and miR expression. We took 2 most complete alternative databases of experimentally validated miR targets--miRTarBase and DianaTarBase, and an OncoFinder database featuring 2725 gene products and 271 signaling pathways. We showed that the impact of miRs is orthogonal to pathway regulation at the mRNA level, which stresses the importance of studying posttranscriptional regulation of gene expression. We also report characteristic set of miR and mRNA regulation features linked with bladder cancer.	bladder
Upper Tract Urothelial Carcinomas Accompanied by Previous or Synchronous Nonmuscle-Invasive Bladder Cancer and Preoperative Hydronephrosis Might Have Worse Oncologic Outcomes After Radical Nephroureterectomy.	BACKGROUND: The purpose of the study was to identify predictors of clinicopathologic features and oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: The medical records of 172 patients treated with RNU from January 2001 to September 2014 were retrospectively reviewed. Logistic regression and survival analysis methodology were respectively used to evaluate predictors of clinicopathologic features and oncologic outcomes. RESULTS: Of the enrolled 172 patients, 80 (46.5%) had renal pelvic tumors, 67 (39%) had ureteral tumors, and the remaining 25 (14.5%) patients had multifocal tumors. Compared with patients with renal pelvic tumors, those with ureteral and multifocal tumors were more likely to have previous or synchronous nonmuscle-invasive bladder cancer (NMIBC) and severe hydronephrosis (P = .001 and P < .001, respectively). Logistic regression analysis showed that previous or synchronous NMIBC was significantly associated with worse renal function and high grade (P = .034 and P = .014, respectively), and severe hydronephrosis independently predicted worse renal function and positive lymph node or lymphovascular invasion status (P = .001 and P = .007, respectively). Moreover, severe hydronephrosis was an independent risk factor for overall survival and cancer-specific survival in multivariate analysis (P = .025 and P = .045, respectively). Multifocality and previous or synchronous NMIBC were significantly associated with bladder-recurrence-free survival (P = .023 and P = .001, respectively). CONCLUSION: Upper tract urothelial carcinoma accompanied by previous or synchronous NMIBC and preoperative severe hydronephrosis could have worse oncologic outcomes after RNU. These common accompanied diagnoses could be valuable for guiding preoperative planning and postoperative adjuvant therapy.	bladder
[Solitary Bladder Metastasis of Chromophobe Renal Cell Carcinoma: Report of a Case].	Bladder metastasis of renal cell carcinoma (RCC) is relatively rare, and only 43 cases have been reported in the Japanese literature. In most cases, the histology of the primary site was clear cell type. Here, we report a case of bladder metastasis of chromophobe RCC. A 74-year-old man presented with asymptomatic gross hematuria. He had a history of chromophobe RCC treated with radical nephrectomy 11 years previously. Since cystoscopy revealed a papillary pedunculated tumor, he underwent transurethral resection of the bladder tumor (TUR-Bt). The pathological diagnosis was chromophobe RCC because the histological findings were similar to those of nephrectomized specimens. Four years after TUR-Bt, the patient received bacillus Calmette-Guérin (BCG) therapy under the diagnosis of carcinoma in situ of urothelial cancer of the bladder but not chromophobe RCC. There was no recurrence of chromophobe RCC within 5 years follow-up after TUR-Bt. To the best of our knowledge, there has been only one other case report of bladder metastasis of chromophobe RCC in the Japanese literature.	bladder